To the Editor We read with interest the Original Investigation by Cowley and colleagues1 in a recent issue of JAMA Internal Medicine on a randomized clinical trial evaluating the efficacy and safety of antiviral therapy for prevention of cytomegalovirus (CMV) reactivation in patients in the intensive care unit (ICU).
This is undoubtedly a relevant topic because CMV reactivation has been associated with prolonged ICU hospitalization and increased mortality in this population group.2 Cowley and colleagues1 claim that antiviral prophylaxis with valacyclovir or low-dose valganciclovir suppresses CMV reactivation in these patients. Nevertheless, the data presented do not fully support this assumption. In fact, while the use of antiviral prophylaxis significantly decreased the incidence of CMV DNAemia and clearly suppressed CMV urine shedding, this was not the case for oral shedding and, of particular importance, for virus replication in the lower respiratory tract (2 patients in the control group and 2 patients in the valganciclovir group had CMV DNA detected in nondirected bronchiolar lavages). Certainly, the limited number of patients screened for the presence of CMV DNA in the lower respiratory tract (28%) does not allow to draw definitive conclusion on this issue, although it raises some concerns as to whether the efficacy of antiviral prophylaxis could be suboptimal in suppressing CMV replication in the lungs. Whether or not CMV replication in the lower respiratory tract can be efficiently blocked by antiviral prophylaxis is of paramount relevance because the deleterious effects of CMV in patients in the ICU, if any, would likely be linked to local virus replication, as it has been shown to occur in the murine CMV model of sepsis.3 In addition, future studies on this subject should consider the fact that CMV replication at the lower respiratory tract may occur in the absence of CMV DNAemia (in up to 25% of patients in the ICU who are CMV seropositive), so that monitoring for the presence of CMV in the blood compartment may underestimate the actual incidence of active CMV infection in this population group.4
Aguilar G, Navarro D. Cytomegalovirus in Patients in the Intensive Care Unit. JAMA Intern Med. 2017;177(10):1542–1543. doi:10.1001/jamainternmed.2017.4398
Customize your JAMA Network experience by selecting one or more topics from the list below.
Create a personal account or sign in to: